No improvements in CD4 count at diagnosis in African patients in last decade

Very high incidence in some populations should guide testing and prevention strategies

Gus Cairns
Published: 04 February 2015

A study by Harvard Medical School has found that the average CD4 count in sub-Saharan African people who are diagnosed with HIV has not risen since 2002. Neither has the average CD4 count on initiation of treatment, which remains well below the AIDS-defining limit of 200 cells/mm3.  The authors call for far more active HIV  testing and facilitated referral programmes, and continued global financial support for HIV testing and treatment.

A second study of a number of different prevalence and incidence surveys conducted by the International AIDS Vaccine Initiative (IAVI) among selected populations in the region shows that annual HIV incidence ranges from zero to 19% according to the population studied, indicating that specific groups should be the subject of testing and referral initiatives. Groups with especially high incidence included the negative partners in sero-different couples, female sex workers (FSWs), men who have sex with men (MSM), young women in certain locations, and specific communities such as fisherfolk on Lake Victoria. Equally, however, surveys of some similar groups in different locations reported low incidence, showing that it may change rapidly and that regular studies should track incidence hotspots.

It was notable that the incidence rate in most populations with high rates fell two- to threefold after the first three months of being included in an incidence survey, showing that clinical referral and monitoring is itself a useful HIV prevention measure.

CD4 count at diagnosis and at start of treatment

The Harvard study looked at CD4 count on diagnosis and at initiation of antiretroviral therapy (ART) in 127 different studies covering over half a million patients between 2002 and 2012. Only six studies looked at CD4 count at both HIV diagnosis and ART initiation in the same patients.

It found that the average CD4 count at HIV diagnosis was 250 cells/mm3 in 2002 and 309 cells/mm3 in 2012. This increase – amounting to a 5.8 cells cells/mm3 increase per year – was not statistically significant.

The average CD4 count at ART initiation actually decreased very slightly, from 152 cells/mm3 in 2002 to 140 cells/mm3 in 2012, well below the AIDS-defining limit of 200 cells/mm3. This decrease was also not significant.  There was no change in CD4 count at initiation after the issue of the World Health Organization’s 2009 treatment guidelines, which changed the recommended CD4 count at which to start ART from 200 to 350 cells/mm3.

There were exceptions to these CD4 figures. When ART was given to pregnant women for the prevention of mother-to-child transmission, the CD4 count at diagnosis and at ART initiation were 395 and 313 cells/mm3 respectively.  

More significantly in terms of general testing and treatment policy, CD4 counts were a lot higher at both diagnosis and ART initiation in so-called ‘active HIV screening’ programmes. This means initiatives such as community-wide screening, community-based combination prevention programmes that include testing, home-testing and home-based testing by visiting health workers.  In active programmes, CD4 counts at diagnosis and initiation were 405 and 268 cells/mm3 respectively. However, only 3.3% of all the people whose CD4 counts were included were involved in studies of such programmes.

South Africa is the one country that had higher CD4 counts on diagnosis in 2012 than 2002: its year-on-year increase in average CD4 count at diagnosis of nearly 40 cells/mm3 a year would appear to be an endorsement of that country’s HIV awareness strategy. However this has not been matched by an increase in CD4 count at ART initiation, which at 123 cells/mm3 averaged over the whole decade is the second-lowest among countries surveyed after Ethiopia.

The researchers comment that there is a relative lack of data post-2010, with only 14% of studies reporting figures from beyond that year: this is because some multi-year studies do not report till the end, so recent improvements in CD4 count at diagnosis and ART initiation could be missed.

HIV prevalence studies

Meanwhile a series of observational studies conducted by IAVI document extremely high HIV prevalence and incidence rates in some populations and surprisingly low ones in others. IAVI runs a project called the African HIV Prevention Partnership that conduct observational studies in different parts of Africa to uncover populations in particular need of prevention intervention. This is work preparatory to creating an African HIV Clinical Research and Prevention Trials Network similar to HPTN in the US.

Their paper looks at three prevalence and ten incidence studies in varied populations in the countries of Uganda, Rwanda, Kenya, Zambia and South Africa.

In the prevalence studies, a variety of populations in Uganda and Kenya were studied including rural communities, clinic attendees, a random whole-area population sample, and in Nairobi female sex workers (FSWs) and their clients.

Groups in which there was particularly high HIV prevalence includes FSWs (20% - in their clients it was 7%), and divorced and widowed people (as opposed to single or married ones), where prevalence was 28% in a Kenyan study, and 22% in a Ugandan one. HIV was also more common in urban versus rural populations: it was 9% urban versus 2% rural people in a Kenyan study, and, in a Ugandan one, 16% versus 10% for people who lived near a highway versus people whose homes were only accessible by foot.

Peak prevalence age was 30-34 in two studies (16.5% in Uganda and 24% in FSWs) and in the non-FSW studies women had higher prevalence than men (in women, 10% and 13% in two studies versus, in men, 5% and 9%).

Condom use, especially irregular use, was actually associated with higher HIV prevalence than not using them at all, but possibly because it was associated with casual sex. In Nairobi FSWs and clients, prevalence was 17.5% in condom users versus 10% in non-users. In Masaka, Uganda prevalence was 10% in people who never used condoms, and also in people who used them more than half the time: but it was 15% in people who used them only occasionally. Prevalence in people with one steady partner was lower (8-11% across studies) than in people who had more than one (14-17%).

Genital ulcer disease (herpes, syphilis and the like - GUD) were associated with 2.5 to four times the prevalence than in people who did not have GUD.

HIV incidence studies – very high rates in some groups

But it was the incidence studies that found continuing high, and in some cases extraordinarily high, rates of ongoing HIV infection in some communities and groups – and low rates in seemingly similar ones.

One of the easiest and most important populations in which to conduct incidence is serodiscordant couples. In most but not all studies of serodiscordant couples annual HIV incidence was higher where the female partner was the initially HIV-negative one. Very high rates were observed in Lusaka, Zambia (9% a year in female partners, 7% in male) and Ndola in the same country (11% in women and 6% in men).

The ‘real-life’ effect of placing the positive partner on ART was documented in one study in Masaka, Uganda where annual HIV incidence in serodiscordant couples was 4% in male partners and 5% in female but only 1% in partners of either gender when the HIV-positive partner was on ART.

In the latter case particularly, much of this continued HIV infection may have come from outside the main relationship: IAVI genotyped all viruses in the HIV positive partners and found that from 20% to 33% of the infections in their studies came from someone other than the main partner, with one exception on Uganda where there were no ‘unlinked’ infections.

Other groups in which very high incidence was found were MSM, with annual incidence rates of 7% and 6% at two places in Kenya and 9.5% at Rustenberg in South Africa;  women in ‘peripheral communities', i.e. irregular housing in Rustenburg (9%) and members of fishing communities in Lake Victoria (10% in women in one Ugandan location and 5% in men).

And yet, at the same time, some groups with very high prevalence did not have a high rate of ongoing HIV infection. Even though HIV prevalence in Nairobi FSWs was high (see above), annual incidence was very low: in rural communities in Masaka where HIV prevalence was 10%, ongoing HIV incidence was so low in the general population that the team shifted their incidence survey to serodiscordant couples and fishing communities. And in one study in Kenya there were no infections observed within discordant couples at all (this study is unpublished so there is as yet no explanation for this).

One striking and near-universal finding was that enrolment into an HIV incidence study brought down incidence in itself. There were astoundingly high HIV incidence rates among some people in the first three months of their involvement in incidence studies: 15% and 19% in HIV-negative women in Zambian serodiscordant couples, 16% in Kenyan MSM, 12% among women with casual partners in South Africa. In all cases, although incidence remained high, it fell 1.5 to 4-fold after the first three months of being in the survey. This phenomenon has been seen in HIV prevention studies before and may be due to regular monitoring and the attention and counselling of healthcare workers.

HIV prevalence in sub-Saharan Africa has been in decline throughout the period of these studies and access to ART has expanded hugely. However what these two studies show is that the HIV epidemic is still very much an ongoing one in some groups in Africa.

The IAVI writers comment that their findings "provide valuable data for prevention trial design and conduct, prevention planning, and service delivery," especially in key affected populations where  there is high HIV incidence "despite regular HIV testing and counselling."

References

Siedner MJ et al. Trends in CD4 count at presentation to care and treatment initiation in sub-Saharan Africa, 2002-2013: a meta-analysis. Clinical Infectious Diseases, e-pub ahead of print: pii: ciu1137. 2014.

Kamali A et al. Creating an African clinical research and prevention trials network: HIV prevalence, incidence and transmission. PLoS One, Doi:10.1371/journal.pone.0116100. 2015.

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